Diabetes affects 340 million people in the world, including 29.1 million individuals in the United States. A complication in diabetic patients is the inability of wounds to heal, which resulted in 73,000 lower-limb amputations in the United States in 2010. The standard treatment for diabetic foot ulcers includes debridement of the wound, treatment of infection with antibiotics, and reducing or eliminating weight pressure from the lower extremities. There is currently no pharmacological therapeutic available that accelerates wound healing without significant adverse effects.
In diabetic patients, high blood sugar triggers prolonged chronic inflammation, with concomitant elevated levels of matrix metalloproteinases (MMPs). The detrimental effect of MMPs in the diseased tissue has been attributed to rapid turnover of potential growth factors, receptors, and the newly formed extracellular matrix, which are essential for wound healing. Hence, wound healing is impaired and delayed in diabetic patients. However, this process is not well understood and the actual instigator MMPs is not known.
MMPs are a family of zinc-dependent endopeptidases that are capable of degrading extracellular matrix components and are involved in tissue remodeling and restructuring. MMPs are expressed as zymogens or pro-MMPs. Activation by proteolytic removal of the N-terminal pro-domain is required for their catalytic functions. Active forms of MMPs are highly regulated by binding of tissue inhibitors of metalloproteinases (TIMPs). MMPs are presumed to play various roles in regulating inflammatory and repair processes, as well as in wound healing.
In view of the inherent problems associated with chronic wounds and wound healing, there is a need for therapeutic compositions that are effective for the treatment of such wounds. There is also a need for selective therapies that are effective to enhance and accelerate the healing process, particularly in diabetic patients.